‫הודעה על החמרה ( מידע בטיחות) בעלון לרופא‬
17.03.14 :‫תאריך‬
Mepact :‫שם תכשיר באנגלית‬
147-07-33425-00
:‫מספר רישום‬
‫ מדיסון פארמה בע"מ‬:‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫בעלון לרופא‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
MEPACT 4 mg powder for suspension
for infusion for concentrate for
dispersion for infusion.
‫טקסט נוכחי‬
MEPACT 4 mg powder for suspension
for infusion
‫פרק בעלון‬
1.NAME OF
THE
MEDICINL
PRODUCT
Paediatric patients
Paediatric patients
4.2 Posology
The safety and efficacy of MEPACT have been The safety and efficacy of MEPACT have been and Method of
established in children from the age of 2 years. Itestablished
is
in children from the age of 2 years. It is Administration
not recommended for use in children below the not recommended for use in children below the
age of 2 due to a lack of data on efficacy and safety
age of 2 due to a lack of data on efficacy and safety
in this age group
in this age group
Paediatric population <2 years
The safety and efficacy of mifamurtide in
children aged 0 to 2 years have not been
established. No data are available.
Elderly patients Adults >30 years
Elderly patients
4.7
4.6
Fertility, Ppregnancy and
lactation
Pregnancy
There are no data from the use of
mifamurtide in pregnant patients women.
Animal studies are insufficient with
respect to reproductive toxicity (see
section 5.3). MEPACT mifanurtide
should not be used not recommended for
Pregnancy and lactation
Pregnancy
There are no data from the use of
mifamurtide in pregnant patients. Animal
studies are insufficient with respect to
reproductive toxicity (see section 5.3).
MEPACT should not be used during
pregnancy and in women not using
effective contraception.
Fertility,
pregnancy and
Lactation
use during pregnancy and in women of
childbearing potential not using effective
contraception.
Lactation Breast-feeding
It is unknown whether mifamurtide is
excreted in human milk. The excretion of
mifamurtide in milk has not been studied
in animals. A decision on whether to
continue/discontinue breast-feeding or to
continue/discontinue therapy should be
made taking into account the benefit of
breast-feeding to the child and the benefit
of MEPACT mifanurtide therapy to the
woman.
Fertility
No dedicated fertility studies have been
conducted with mifamurtide (see section
5.3).
Lactation
It is unknown whether mifamurtide is
excreted in human milk. The excretion of
mifamurtide in milk has not been studied
in animals. A decision on whether to
continue/discontinue breast-feeding or to
continue/discontinue therapy should be
made taking into account the benefit of
breast-feeding to the child and the benefit
of MEPACT therapy to the woman.
Undesirable effects
Summary of the safety profile
Mifamurtide was studied as a single
agent in Each of the 248 patients treated
with mostly advanced malignancies
MEPACT during the early single arm
phase single arm I and II clinical studies
in patients with mostly advanced
malignancies experienced at least one
undesirable effect.
The most frequent adverse reactions,
occurring in >50% of patients, were
chills, pyrexia, fatigue, nausea,
tachychardia and headache. Many of the
most frequently very commonly reported
undesirable effects adverse reactions as
shown in the following summary table
are thought to be related to the
mechanism of action of mifamurtide (see
Table 1). The majority of these events
were reported as either mild or moderate.
This profile is consistent whether
summarising all early studies (n=248) or
only those studies in osteosarcoma
(n=51). It is likely that these undesirable
effects adverse reactions also occurred in
the large randomised study, but they
were not recorded because only serious
and life-threatening adverse reactions
were collected in that study.
Undesirable effects
Each of the 248 patients treated with
MEPACT during the early phase single
arm studies in patients with mostly
advanced malignancies experienced at
least one undesirable effect. Many of the
most frequently reported undesirable
effects as shown in the following
summary table are thought to be related to
the mechanism of action of mifamurtide.
The majority of these events were
reported as either mild or moderate. This
profile is consistent whether summarising
all early studies (n=248) or only those
studies in osteosarcoma (n=51). It is
likely that undesirable effects also
occurred in the large randomised study,
but they were not recorded because only
serious and life-threatening adverse
reactions were collected in that study.
Blood and lymphatic system disorders
Anaemia has most very commonly been
reported when MEPACT mifanurtide is
used in conjunction with
chemotherapeutic agents. In a
randomised controlled trial study, the
incidence of myeloid malignancy (acute
myeloid leukaemia/myelodysplastic
syndrome) was the same in patients
receiving MEPACT plus chemotherapy
as in patients receiving only
chemotherapy (approximately 2.15%).
Blood and lymphatic system disorders
Anaemia has most commonly been
reported when MEPACT is used in
conjunction with chemotherapeutic
agents. In a randomised controlled trial,
the incidence of myeloid malignancy
(acute myeloid
leukaemia/myelodysplastic syndrome)
was the same in patients receiving
MEPACT plus chemotherapy as in
patients receiving only chemotherapy
(approximately 2.5%).
Metabolism and nutritional disorders
Anorexia (21%) was very commonly
reported in trials of MEPACT in late
stage cancer patients phase I and II
Metabolism and nutritional disorders
Anorexia (21%) was very commonly
reported in trials of MEPACT in late
stage cancer patients.
Undesirable
effects
studies of mifamurtide.
Nervous system disorders
Consistent with other generalised symptoms,
the most common nervous system disorders
were headache (50%) and dizziness (17%).
One patient in the phase III study
experienced 2 episodes of Grade 4 seizure
while on study therapy with chemotherapy
and mifamurtide. The second episode
involved multiple grand mal seizures over the
course of days. Mifamurtide treatment was
continued for the remainder of the study
without seizure recurrence.
Nervous system disorders
Consistent with other generalised
symptoms, the most common nervous
system disorders were headache (50%)
and dizziness (17%).
Cardiac and vascular disorders
Cardiac and vascular disorders
Mild-moderate
tachycardia (50%), hypertension
Mild-moderate tachycardia (50%),
(26%) and hypotension (29%) were commonly
hypertension (26%) and hypotension
(29%) were very commonly reported in
reported in uncontrolled trials of MEPACT.
uncontrolled trials studies of MEPACT
mifanurtide. One serious incident of
subacute thrombosis was reported in
early studies, but no serious cardiac
events were associated with MEPACT
mifanurtide in a large randomised
controlled trial study.
Musculoskeletal and connective tissue
disorders
Low grade pain was very common in
patients receiving MEPACT
mifanurtide, including myalgia (31%),
back pain (15%), extremity pain (12%)
and arthralgia (10%).
Immune system disorders
In a phase I study, there was one report of
severe allergic reaction occurring after the
first infusion of mifamurtide at 6 mg/m2 dose
level. The patient experienced shaking, chills,
fever, nausea, vomiting, uncontrollable
coughing, shortness of breath, cyanotic lips,
dizziness, weakness, hypotension,
tachycardia, hypertension and hypothermia
leading to study discontinuation. There was
also one report of a grade 4 allergic reaction
(hypertension) requiring hospitalization in
the phase III study (see section 4.4).
Musculoskeletal and connective tissue
disorders
Low grade pain was common in patients
receiving MEPACT, including myalgia
(31%), back pain (15%), extremity pain
(12%) and arthralgia (10%).
‫לא קיים‬
‫לא קיים‬
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after
authorisation of the medicinal product is
important. It allows continued monitoring of
the benefit/risk balance of the medicinal
product. Healthcare professionals are asked
to report any suspected adverse reactions.
5.1
Pharmacodynamic properties
Pharmacotherapeutic group:
Immunostimulants, Other
immunostimulants, Other cytokines and
immunomodulators, ATC code:
L03AX15
Nature and contents of container
5.1
Pharmacodynamic properties
Pharmacodyna
mic properties
Pharmacotherapeutic group: Other
cytokines and immunomodulators, ATC
code: L03AX15
Nature and contents of container
50 ml type I glass vial with a grey butyl
rubber stopper, aluminium seal and
plastic flip-off cap, containing 4 mg of
mifamurtide.
50 ml type I glass vial with a grey butyl
rubber stopper, aluminium seal and
plastic flip-off cap, containing 4 mg of
mifamurtide.
Each carton contains one vial and one
single-use, non-pyrogenic, latex-free
sterile Ffilter for MEPACT supplied in a
PVC-grade blister.
Each carton contains one vial and one
single-use, non-pyrogenic, latex-free
sterile Filter for MEPACT supplied in a
PVC-grade blister.
Nature and
contents of
container
.‫ שבו מסומנות ההחמרות המבוקשות על רקע צהוב‬,‫מצ"ב העלון‬
‫ יש לסמן רק תוכן מהותי ולא שינויים‬.‫שינויים שאינם בגדר החמרות סומנו (בעלון) בצבע על רקע ירוק‬
.‫במיקום הטקסט‬